Sudden cardiac death due to ventricular fibrillation (VF) remains one of our nation's major health problems. When VF is terminated immediately by appropriate defibrillation techniques, the patient has an excellent chance for long-term survival. An understanding of electrophysiological factors influencing the development of VF and its maintenance as well as the mechanism and factors favoring defibrillation is of immediate importance to help develop therapeutic regimes for preventing sudden cardiac death due to primary VF. One of the most extensively employed experimental techniques for studying VF in animals is the measurement of the minimal current which when passed through the ventricular myocardium initiates VF; this measurement is referred to as the ventricular fibrillation threshold (VFT). Recent preliminary data from our laboratory suggests that the VFT technique as employed in animal models qualitatively predicts the VFT in man. We recently found problems with the VFT technique: a) different results are sometimes obtained using a train of pulses vs. a single pulse when testing vulnerability and b) time lag between applying a control VFT train gives variable results. We feel it necessary to investigate the discrepancy between the two VFT techniques and to further evaluate the mechanism by which the VFT technique induces VF. Both intracellular and extracellular recording and stimulating techniques will be utilized in combination with two new techniques available in our laboratory: 1) a potassium sensitive electrode to record extracellular potassium concentrations and 2) a non-invasive technique for evaluating cardiac ischemia using nicotinamide adenine dinucleotide fluorescent photography. Although techniques for studying initiation of VF have provided considerable new information, a similar technique evaluating defibrillation, i.e., a defibrillation threshold technique has not been developed. We propose to develop a defibrillation threshold technique. The proposed studies will provide basic new information to help develop and evaluate new methods for preventing sudden cardiac electrical deaths in man.